ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.938C>T (p.Pro313Leu)

gnomAD frequency: 0.00004  dbSNP: rs748388661
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238113 SCV002009669 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001885121 SCV002175525 uncertain significance Aortic valve disease 2 2021-11-16 criteria provided, single submitter clinical testing This variant is present in population databases (rs748388661, gnomAD 0.02%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1319866). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 313 of the SMAD6 protein (p.Pro313Leu).
Ambry Genetics RCV002370311 SCV002686394 uncertain significance Inborn genetic diseases 2022-05-09 criteria provided, single submitter clinical testing The p.P313L variant (also known as c.938C>T), located in coding exon 3 of the SMAD6 gene, results from a C to T substitution at nucleotide position 938. The proline at codon 313 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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